Use of piperidine derivatives as dermo-decontracting agents

ABSTRACT

The present invention relates to a cosmetic process for treating wrinkled skin, in particular the skin of the face and/or of the forehead, through a dermo-decontracting effect, comprising the topical application to said skin of a composition comprising, in a physiologically acceptable medium, at least one piperidine derivative chosen from the compounds of formula (I): 
     
       
         
         
             
             
         
       
     
     These compounds make it possible to combat expression wrinkles according to a mechanism of dermo-decontraction.

The present invention relates to a cosmetic process for treatingwrinkled skin through a dermo-decontracting effect, comprising thetopical application to said skin of a composition comprising, in aphysiologically acceptable medium, at least one piperidine derivative ofspecific formula.

Women, and even men, currently have a tendency to wish to look youthfulfor as long as possible and consequently seek to fade out the signs ofage on the skin, which are reflected in particular by wrinkles and finelines. In this respect, advertising and the fashion world talk aboutproducts intended to keep the skin radiant and wrinkle-free, which aresigns of youthful skin, for as long as possible, and all the more sosince the physical appearance has an effect on the psyche and/or on themorale.

Up until now, wrinkles and fine lines were treated using cosmeticproducts containing active agents acting on the skin, for example byimproving its cell renewal or alternatively by promoting the synthesisof, or by preventing the degradation of, the elastic fibres of whichskin tissue is composed.

Although these treatments make it possible to act on the wrinkles andfine lines caused by chrono-logical or intrinsic ageing, and also onthose caused by photoageing, they have no effect on expression wrinkles,which require an intervention on the muscular contractile component (viamuscle-relaxing agents) or dermal contractile component (viadermo-decontracting agents) of wrinkles.

Expression wrinkles are in fact the result of mechanisms that aredifferent from those that generate wrinkles caused by ageing.

Specifically, they are produced due to the effect of the strain exertedon the skin by the skin muscles that allow facial expressions. Dependingon the shape of the face, the frequency of facial expressions andpossible tics, they may appear as early as childhood. Age, along withcertain environmental factors such as exposure to sunlight, are notinvolved in generating them, but may make them deeper and permanent.

Expression wrinkles are characterized by the presence of grooves aroundthe orifices formed by the nose (nasal grooves), the mouth (perioralwrinkles and “sour-face” wrinkles) and the eyes (crow's-feet wrinkles),around which are the skin muscles, and also between the eyebrows(glabella wrinkles or lion wrinkles) and on the forehead.

Until now, the only means commonly used for acting on expressionwrinkles is botulinum toxin, which is in particular injected into thewrinkles of the glabella, which are wrinkles between the eyebrows (seeJ. D. Carruters et al., J. Dermatol. Surq. Oncol., 1992, 18, pp. 17-21).

The applicant has also proposed various compounds capable of providing amuscle-relaxing effect when they are applied topically to the skin, thusmaking it possible to act on expression wrinkles via another route.Among these compounds, mention may in particular be made of calciumchannel-associated receptor antagonists, such as verapamil (FR-2 793681), and in particular manganese and its salts (FR-2 809 005), andalverine (FR-2 798 590); chloride channel-associated receptor agonists,including glycine (EP-0 704 210) and certain extracts of Iris pallida(FR-2 746 641); and sapogenins (EP-1 352 643).

Along with these muscle-relaxing agents, the applicant has describedvarious dermo-decontracting compounds, and in particular amine compounds(EP-1 405 633).

However, there is still a need for compounds that are more effectivethan those of the prior art for smoothing or fading out expressionwrinkles.

Now, the applicant has discovered, surprisingly, that certain piperidinederivatives can satisfy this need. Specifically, it has beendemonstrated that these compounds make it possible to relax ordecontract the dermal contractile cells that are supposed to be involvedin generating expression wrinkles. It is in fact thought that thephenotype of certain fibroblasts located along the tension lines createddue to skin muscle contractions during facial expressions is graduallymodified under the effect of these contractions, thus conferringspecific contractile properties on these fibroblasts. The decontractionof these cells will thus make it possible to act on another component ofexpression wrinkles.

Among the compounds used according to the invention, several havealready been described as calcium channel inhibitors in applicationsEP-0 542 846 and JP-61 027 963 and in U.S. Pat. No. 4,952,560.

However, the applicant had demonstrated that, while calcium channelinhibitors are, a priori, muscle relaxing agents according to theteaching of application FR-2 793 681, they are not alldermo-decontracting agents. In particular, cinnarizine, diltiazem,nitrendipine and diazepam, which are known anti-calcium compounds(either because they act directly on calcium channels or because theyact on chloride channels and thus generate an anti-calcium effect) andthe muscle relaxing effect of which has—at least as regardsdiazepam—been demonstrated, are not active as dermo-decontracting agentsin the test presented in Example 1 hereinafter. It was not thereforepossible to predict that the compounds used according to the presentinvention, also known as calcium channel inhibitors, would have adermo-decontracting effect.

In addition, dermo-decontraction is a phenomenon that results from thephosphorylation of the myosin light chain. This phosphorylation ismodulated by many factors, for instance the activity of the myosin lightchain-specific phosphatase. Now, calcium channel inhibitors do notaffect this pathway. There is therefore nothing that implies that someof these inhibitors may have a dermo-decontracting effect.

Among the compounds used according to the present invention, ifenprodilhas already been described as an anti-glycation agent for the treatmentof age-, diabetes- and smoking-related complications (WO 03/032969), forpromoting blood circulation and moisturizing the skin (JP-62 226 909 andU.S. Pat. No. 4,952,560) and in hair products (JP-62 270 514). Otherpiperidine derivatives have been described as antibacterial agents (EP-0308 328).

On the other hand, to the applicant's knowledge, the use of thesepiperidine derivatives for combating wrinkles, in particular expressionwrinkles, and/or for decontracting the skin and/or relaxing thefeatures, has never been suggested.

A subject of the present invention is therefore a cosmetic process fortreating wrinkled skin, in particular the skin of the face and/or of theforehead, through a dermo-decontracting effect, comprising the topicalapplication to said skin of a composition comprising, in aphysiologically acceptable medium, at least one piperidine derivativechosen from the compounds of formula (I):

in which:R₁ denotes a halogen or a radical chosen from: a C₁-C₆ alkyl radical, anOR group, an NRR′ group, a CF₃ group, an NHCOR group or a CONRR′ group;R₂ denotes a linear or branched C₁-C₂₀ alkyl or alkenyl radicaloptionally substituted with at least one OR, COOR, ═O, NRR′, NHCOR orCONRR′ group or with a phenyl group optionally substituted with one ormore radicals R₁;

where R and R′ denote, independently of one

another, a hydrogen atom or a C₁-C₆ alkyl radical,

m ranges from 0 to 5;n ranges from 0 to 5;and their salts and optical isomers.

A subject of the invention is also the cosmetic use of at least onepiperidine derivative as defined above, as a dermo-decontracting agentfor combating wrinkles, in particular expression wrinkles, and/or fordecontracting the skin and/or relaxing the features.

In formula (I), the alkyl groups may in particular be chosen, accordingto the case, from the groups: methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl,decyl, undecyl, dodecyl, myristyl, palmityl, stearyl and arachidyl.

In addition, in the context of this application, the term “alkenyl” isintended to mean radicals possibly comprising one or more double bonds,that may or may not be conjugated. They may in particular be chosen,according to the case, from the groups: vinyl, allyl, butenyl orpentenyl.

As salts of the compound of formula (I), mention may be made of thesalts obtained by addition of the compound of formula (I) with aninorganic acid, chosen in particular from hydrochloric acid, sulphuricacid and phosphoric acid, or with an organic acid, chosen in particularfrom acetic acid, propionic acid, succinic acid, fumaric acid, maleicacid, lactic acid, glycolic acid, citric acid and tartaric acid.

Preferably, the piperidine derivative according to the invention is suchthat at least one, and preferably all, of the following conditions aresatisfied:

-   -   m ranges from 0 to 3, and is preferably equal to 0,    -   n is equal to 0 or 1,    -   R₁ denotes a methoxy radical or trifluoromethyl radical,    -   R₂ denotes a linear or branched C₁-C₆ alkyl or alkenyl radical        optionally substituted with a phenyl group.

It is advantageously 4-phenyl-1-(4-phenylbutyl)piperidine or one of itssalts, such as its maleic acid salt (commercially available), or else4-benzyl-1-hexylpiperidine or one of its salts.

The compounds of formula (I) can in particular be prepared according tothe following reaction scheme:

by reacting one equivalent of substituted piperidine A with oneequivalent of B, where X denotes a leaving group of halogen orsulphonate type, in the presence of K₂CO₃ in acetonitrile at refluxovernight. The product obtained can be treated and purified on a silicacolumn.

The amount of piperidine derivative that can be used according to theinvention depends of course on the desired effect and can therefore varyto a large extent.

To give an order of magnitude, these derivatives can be used in anamount representing from 0.01% to 10% of the total weight of thecomposition, preferably in an amount representing from 0.05% to 5% ofthe total weight of the composition, more preferably in an amountrepresenting from 0.1% to 2% of the total weight of the composition.

The composition used according to the invention is suitable for topicalapplication to the skin, and it therefore contains a physiologicallyacceptable medium, i.e. a medium that is compatible with the skin andoptionally with its integuments (eyelashes, nails, hair) and/or themucous membranes. This medium is advantageously cosmetically acceptable,i.e. it does not result in itching, stinging or redness that may put offthe user of the composition, and it has a pleasant appearance, smell andfeel.

This composition may be provided in any of the pharmaceutical formsnormally used in the cosmetics field, and in may in particular be in theform of an optionally gelled solution, of a dispersion of the lotiontype, optionally a two-phase lotion, of an emulsion obtained bydispersion of a fatty phase in an aqueous phase (O/W) or vice versa(W/O), or of a triple emulsion (W/O/W or O/W/O) or of a vesiculardispersion of ionic and/or non-ionic type. These compositions areprepared according to the usual methods. According to this invention, itis preferable to use a composition in the form of an oil-in-wateremulsion.

This composition may be more or less fluid and may have the appearanceof a white or coloured cream, of an ointment, of a milk, of a lotion, ofa serum, of a paste or of a mousse. It may optionally be applied in theform of an aerosol. It may also be provided in solid form, in particularin the form of a stick. It may be used as a care product and/or as amakeup product for the skin.

In a known manner, the composition used according to the invention mayalso contain the adjuvants that are usual in the cosmetics field, suchas hydrophilic or lipophilic gelling agents, hydrophilic or lipophilicactive agents, preserving agents, antioxidants, solvents, fragrances,fillers, screening agents, pigments, odour absorbers and dyes. Theamounts of these various adjuvants are those conventionally used in thefield under consideration, and for example from 0.01 to 20% of the totalweight of the composition. Depending on their nature, these adjuvantsmay be introduced into the fatty phase, into the aqueous phase or intothe lipid vesicles. In any event, these adjuvants, and the proportionsthereof, will be chosen so as not to harm the desired properties of thepiperidine derivatives according to the invention.

When the composition used according to the invention is an emulsion, theproportion of the fatty phase may range from 5 to 80% by weight, andpreferably from 5 to 50% by weight, relative to the total weight of thecomposition. The oils, the emulsifiers and the co-emulsifiers used inthe composition in the form of an emulsion are chosen from thoseconventionally used in the field under consideration. The emulsifier andthe co-emulsifier are present in the composition in a proportion rangingfrom 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight,relative to the total weight of the composition.

As oils that may be used in the invention, mention may be made ofmineral oils (liquid petroleum jelly), oils of plant origin (avocadooil, soybean oil), oils of animal origin (lanolin), synthetic oils(perhydrosqualene), silicone oils (cyclomethicone) and fluoro oils(perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids orwaxes (carnauba wax, ozokerite) may also be used as fats.

As emulsifiers and co-emulsifiers that may be used in the invention,mention may, for example, be made of fatty acid esters of polyethyleneglycol, such as PEG-100 stearate, and fatty acid esters of glycerol suchas glyceryl stearate.

As hydrophilic gelling agents/thickeners, mention may in particular bemade of carboxyl vinyl polymers (carbomer), acrylic copolymers such asacrylate/alkyl acrylate copolymers, polyacrylamides, polysaccharides,natural gums and clays, and as lipophilic gelling agents/thickeners,mention may be made of modified clays such as bentones, metal salts offatty acids, and hydrophobic silica.

As active agents, it will be advantageous to introduce into thecomposition used according to the invention at least one compound chosenfrom: desquamating agents; moisturizers; depigmenting or propigmentingagents; anti-glycation agents; NO-synthase inhibitors; agents forstimulating the synthesis of dermal or epidermal macromolecules and/orfor preventing their degradation; agents for stimulating fibroblastand/or keratinocyte proliferation or for stimulating keratinocytedifferentiation; the other muscle-relaxing agents and/or otherdermo-decontracting agents; tensioning agents; antipollution agentsand/or free-radical scavengers; agents that act on the microcirculation;agents that act on the energy metabolism of cells; and mixtures thereof.

Examples of such additional compounds are: retinol and its derivativessuch as retinyl palmitate; ascorbic acid and its derivatives such asmagnesium ascorbyl phosphate and ascorbyl glucoside; tocopherol and itsderivatives such as tocopheryl acetate; nicotinic acid and itsprecursors such as nicotinamide; ubiquinone; glutathione and itsprecursors such as L-2-oxothiazolidine-4-carboxylic acid; plant extractsand in particular plant proteins and hydrolysates thereof, and alsophytohormones; marine extracts such as algal extracts; bacterialextracts; sapogenins, such as diosgenin, and extracts of Wild Yamcontaining them; ceramides; hydroxy acids; hydroxy acids such assalicylic acid and 5-n-octanoylsalicylic acid; resveratrol;oligopeptides and pseudopeptides and acylated derivatives thereof;manganese salts and magnesium salts, in particular gluconates; andmixtures thereof.

As indicated above, the composition according to the invention may alsocontain photoprotective agents that are active in the UVA and/or the UVBrange, in the form of organic or inorganic compounds, the latter beingoptionally coated in order to make them hydrophobic.

The organic photoprotective agents can in particular be chosen from:anthranilates, in particular menthyl anthranilate; benzophenones, inparticular benzophenone-1, benzophenone-3, benzophenone-5,benzophenone-6, benzophenone-8, benzophenone-9, benzophenone-12, andpreferably benzophenone-3 (oxybenzone), or benzophenone-4 (Uvinul MS40available from BASF); benzylidenecamphors, in particular3-benzylidenecamphor, benzylidenecamphorsulphonic acid, camphorbenzalkoniummethosulphate, polyacrylamidomethylbenzylidenecamphor,terephthalylidinedicamphorsulphonic acid, and preferably4-methylbenzylidenecamphor (Eusolex 6300 available from Merck);benzimidazoles, in particular benzimidazilate (Neo Heliopan AP availablefrom Haarmann and Reimer), or phenylbenzimidazolesulphonic acid (Eusolex232 available from Merck); benzotriazoles, in particular drometrizoletrisiloxane, or methylenebisbenzotriazolyltetramethylbutylphenol(Tinosorb M available from Ciba); cinnamates, in particular cinoxate,DEA methoxycinnamate, diisopropyl methylcinnamate, glycerylethylhexanoate dimethoxycinnamate, isopropyl methoxycinnamate, isoamylcinnamate and, preferably, ethocrylene (Uvinul N35 available from BASF),octyl methoxycinnamate (Parsol MCX available from Hoffmann La Roche), oroctocrylene (Uvinul 539 available from BASF); dibenzoylmethanes, inparticular butylmethoxydibenzoylmethane (Parsol 1789); imidazolines, inparticular ethylhexyl dimethoxybenzylidene dioxoimidazoline; PABAs, inparticular ethyl dihydroxypropyl PABA, ethylhexyldimethyl PABA, glycerylPABA, PABA, PEG-25 PABA and, preferably, diethylhexylbutamidotriazone(Uvasorb HEB available from 3V Sigma), ethylhexyltriazone (Uvinul T150available from BASF) or ethyl PABA (benzocaine); salicylates, inparticular dipropylene glycol salicylate, ethylhexyl salicylate,homosalate or TEA salicylate; triazines, in particular anisotriazine(Tinosorb S available from Ciba).

The inorganic photoprotective agents preferably consist of zinc oxideand/or titanium dioxide, preferably of nanometric size, optionallycoated with alumina and/or stearic acid.

The composition according to the invention is advantageously intended tobe applied to areas of the face and/or of the forehead that are markedwith expression wrinkles, and/or on individuals with expressionwrinkles.

The wrinkles concerned are preferably those lying radially around themouth and/or the eyes, in particular the crow's-feet wrinkles, and/orlying on the forehead, in particular the “lion” wrinkle, located in theglabella, in between the eyebrows, and/or lying horizontally on theforehead.

The invention will now be illustrated by means of the followingnon-limiting examples. In these examples, the amounts are indicated aspercentages by weight.

EXAMPLES Example 1 Demonstration of the Dermo-Decontracting Effect ofthe Piperidine Derivatives According to the Invention a) Principle ofthe Test

The principle of this test consists in studying the decontracting effectof the maleic acid salt of 4-phenyl-1-(4-phenylbutyl)piperidine(commercially available from one of the companies Biomol, ICN, Nacalaiand Tocris), on a dermis equivalent model consisting of a matrix ofcollagen seeded with normal human fibroblasts.

These conditions are intended to mimic, in vitro, the dermal contractilephenomena that occur during facial expressions. Under these conditions,in fact, the cells spontaneously express tensile forces that induce aretraction of the collagen gel. As a result of this, there is a decreasein the total surface area of the dermis equivalent over time.Measurement of this surface area makes it possible to evaluate therelaxing effects of the substances brought into contact with the dermisequivalent beforehand.

b) Protocol

Two series of attached dermis equivalents containing normal humanfibroblasts are prepared: a control series without any treatment, and aseries treated with the test compound (1 μM). The experiment is repeatedthree times.

The dermis equivalents are prepared as described in Asselineau et al.,Exp. Cell. Res., 1985, 159, 536-539; Models in dermatology, 1987, Vol. 3pp. 1-7, in the following proportions:

MEM medium (1.76X) with or without compound 45% Foetal calf serum: 10%NaOH (0.1N): 5% Acetic acid (1/1000): 4% Collagen: 26% Fibroblasts: 11%

The treated dermis equivalent differs from the control dermisequivalents in that 1 μM of the test compound is added thereto.

The collagen used is type I collagen (commercial solution). It isextracted from rat tails or from calf skin by acid hydrolysis and isconserved in an acidic medium at +4° C.; it polymerizes naturally byreheating to 37° C. and by a decrease in the degree of acidity. Thecollagen is dialysed beforehand against successive baths of water+aceticacid.

The protocol is as follows: the 1.76×MEM medium in the presence ofadditives (1% glutamine, 1% nonessential amino acids, 1% sodiumpyruvate, 1% fungizone and 1% Penicillin/Streptomycin), the foetal calfserum and the 0.1 N sodium hydroxide NaOH are introduced into a 50 mlcentrifuge tube kept in crushed ice. The fibroblasts isolated form humanskin explants are then added at a concentration of 1.5×10⁵ cells per 1ml of culture medium.

A volume/volume mixture of collagen in acetic acid at 1/1000 is thenadded slowly, along the wall of the tube so as to observe the appearanceof a whitish cloud.

The entire combination is then carefully mixed and dispensed into thewells of a 12-well culture plate (Costar type, reference 3512) in aproportion of 2 ml of mixture per well. The final cell concentration is3×10⁴ cells/dermis equivalent, with a final collagen concentration of 1mg/ml. The culture plate is then placed in an incubator at 37° C. with5% CO₂.

Once formed after polymerization of the collagen, the dermis equivalentsare left adherent to the culture support for 3 days and are thendetached from the support so that the contraction may begin. Theseattached dermis equivalents are taken out of the incubator in order totake the pictures for the purpose of measuring their surface area, foreach point of the contraction kinetics (0, 4, 8 and 24 hours). They areimmediately returned to the incubator between each measurement point.

The spontaneous contraction of the dermis equivalent that is treated(with the test compound) and the control dermis equivalent (without testcompound) is evaluated by measuring their surface area, at various timesafter the beginning of the spontaneous contraction.

For this, a digital image is acquired for each treated or nontreateddermis equivalent, by means of a camera (CCD camera—Iris Sony DXC—107P)and the surface area is then calculated on each image by means of animage analysing system (Zeiss Axiovision 3.0). Correspondent to thissurface area measurement is a percentage contraction equal to the ratioof the surface areas according to the formula:

% contraction=(Sp−Si)/Sp×100

where:‘Sp’ represents the surface area of a well of the culture plate; itcorresponds to the total surface area of the dermis equivalent beforecontraction,‘Si’ represents the surface area of the dermis equivalent at the momenti of the contraction kinetics.

c) Results

The maleic acid salt of 4-phenyl-1-(4-phenylbutyl)piperidine reduces thecontraction of the fibroblasts by 17%, on average, over the duration ofthe experiment, compared with the control. This compound therefore has asignificant dermo-decontracting effect.

Example 2 Synthesis of 4-phenyl-1-(4-phenylbutyl)piperidine

This compound was prepared according to the following reaction scheme:

4-Phenylpiperidine (1 eq) was reacted with 4-phenylbromobutyl (1 eq) inthe presence of K₂CO₃ in acetonitrile at reflux overnight. The productobtained was treated and purified on a silica column. The ¹H NMR at 500MHz is in accordance with the expected structure.

Example 3 Cosmetic Composition

This composition is prepared in a manner that is conventional for thoseskilled in the art. The amounts given in this example are indicated aspercentages by weight.

4-Phenyl-1-(4-phenylbutyl)piperidine 0.10% Stearic acid 3.00% Mixture ofglyceryl monostearate and 2.50% polyethylene glycol stearate (100 EO)Polyethylene glycol stearate (20 EO) 1.00% Cyclopentadimethylsiloxane10.00% Fillers 3.00% Plant oils 7.00% Synthetic oils 6.00% Preservingagents 1.20% Oxyethylenated (16 EO) dimethylsiloxane 1.00% with methoxyends Silicone gum 0.20% Acrylic copolymer in an inverse emulsion 1.70%(Simulgel 600 from Seppic) Stearyl alcohol 1.00% Water qs 100%

This cream is intended to be applied to the face and the forehead inorder to relax the features and decontract the facial skin.

1. Cosmetic process for treating wrinkled skin, in particular the skinof the face and/or of the forehead, through a dermo-decontractingeffect, comprising the topical application to said skin of a compositioncomprising, in a physiologically acceptable medium, at least onepiperidine derivative chosen from the compounds of formula (I):

in which: R₁ denotes a halogen or a radical chosen from: a C₁-C₆ alkylradical, an OR group, an NRR′ group, a CF₃ group, an NHCOR group or aCONRR′ group; R₂ denotes a linear or branched C₁-C₂₀ alkyl or alkenylradical optionally substituted with at least one OR, COOR, ═O, NRR′,NHCOR or CONRR′ group or with a phenyl group optionally substituted withone or more radicals R₁; where R and R′ denote, independently of oneanother, a hydrogen atom or a C₁-C₆ alkyl radical, m ranges from 0 to 5;n ranges from 0 to 5; and their salts and optical isomers.
 2. Processaccording to claim 1, characterized in that said salt is a salt obtainedby addition of the compound of formula (I) with an inorganic acid chosenfrom hydrochloric acid, sulphuric acid and phosphoric acid.
 3. Processaccording to claim 1, characterized in that said salt is a salt obtainedby addition of the compound of formula (I) with an organic acid chosenfrom acetic acid, propionic acid, succinic acid, fumaric acid, maleicacid, lactic acid, glycolic acid, citric acid and tartaric acid. 4.Process according to any one of claims 1 to 3, characterized in thatsaid derivative is such that m ranges from 0 to
 3. 5. Process accordingto any one of claims 1 to 4, characterized in that said derivative issuch that R₁ denotes a methoxy or trifluoromethyl radical.
 6. Processaccording to claim 4, characterized in that said derivative is such thatm is equal to
 0. 7. Process according to any one of claims 1 to 6,characterized in that said derivative is such that R₂ denotes a linearor branched C₁-C₆ alkyl or alkenyl radical optionally substituted with aphenyl group.
 8. Process according to any one of claims 1 to 7,characterized in that said derivative is such that n is equal to
 0. 9.Process according to any one of claims 1 to 8, characterized in thatsaid derivative is 4-phenyl-1-(4-phenylbutyl)piperidine or one of itssalts.
 10. Process according to claim 9, characterized in that saidderivative is the maleic acid salt of4-phenyl-1-(4-phenylbutyl)piperidine.
 11. Process according to any oneof claims 1 to 7, characterized in that said derivative is such that nis equal to
 1. 12. Process according to claim 11, characterized in thatsaid derivative is 4-benzyl-1-hexylpiperidine.
 13. Process according toany one of claims 1 to 12, characterized in that the composition isapplied to the areas of the face and/or of the forehead that are markedwith expression wrinkles, and/or on individuals with expressionwrinkles.
 14. Cosmetic use of at least one piperidine derivative asdefined in any one of claims 1 to 12, as a dermo-decontracting agent forcombating wrinkles, in particular expression wrinkles, and/or fordecontracting the skin and/or relaxing the features.